Brain matter is composed of neurons and glia. Neurons are individual nerve cells that convey and integrate information such as thought, feeling, and action to other neurons, muscles, organs, and glands. There are an estimated 86 billion neurons in the human brain. Neurons are composed of;

• Cell body: filled with cytoplasm which suspends a number of organelles, notably the nucleus

• Dendrites: extensions that branch out from the neural cell body to receive information from other neurons.

• Axon: an extension from a neuron’s cell body that carries information to other locations and is wrapped in the myelin sheath.

• Axon terminals: end bulbs on the end of a neuron that contains neurotransmitters.

• Axon hillock: where the axon joins the cell body.

• Myelin: a fatty tissue that wraps around an axon to insulate it from the surrounding fluid and other neurons. Myelin is produced in the brain and spinal cord by glial cells called oligodendrocytes and in the rest of the nervous system by Schwann cells.

• Myelin sheath: a fatty layer of myelin that insulates a neuron’s axon and speeds electrical impulses.

• Node of Ranvier: periodic gaps in the myelin sheath on the axon that certain neurons use to facilitate the rapid conduction of action potentials. The gaps allow ions to quickly diffuse in and out of the neuron, propagating the electrical signal down the axon. Because there are few sodium channels under the myelin sheath, action potentials cannot occur there, but in the nodes, there are many sodium channels in which the graded potential triggers an action potential that appears to jump from node to node in a form of transmission called saltatory conduction — the flow of electricity down the axon in which action potentials jump from one node of Ranvier to the next.

• Neurotransmitters: a chemical substance released by a neuron that binds to receptors on the same neuron, nearby neurons, or other tissues such as muscles and organs.

Types of Neurons

• Motor neurons: carry commands to the muscles and organs. A multipolar neuron, meaning its dendrites branch in several directions from the cell body. Also called efferent neurons, they carry motor information from the CNS to the rest of the body.

• Sensory neurons: carry information from the body and external stimuli into the CNS. Can be unipolar, meaning a single short stalk from the cell body that divides into two branches, or bipolar, meaning axon and dendritic processes are on opposite sides of the cell body. Also called afferent neurons, they carry sensory information from the rest of the body to the CNS.

• Interneurons: neurons that have short axons or no axons at all and connect one neuron to another in the same part of the CNS. Is specialized for making connections over short distances and multipolar.

Glia

Glia (Greek for glue) are nonneural cells that produce several supporting functions for neurons, including myelination —Myelination decreases capacitance, an electrical effect that slows the movement of ions down the axon, which grants the graded potential a speed boost. The nodes of Ranvier cause the signal to be regenerated by an action potential at every node. Myelinated neurons use much less energy because there is less work for the sodium-potassium pump to do.

Types of Glia

• Astrocytes: (pl. astroglia) star-shaped glial cells in the CNS that regulate homeostasis of extracellular fluid, ions, and transmitter, and the regulation of synapse function, and synaptic remodeling.

• Microglia: glial cells that function as macrophages in the CNS.

• Radial glial cells: (RGCs) distinct nonneural cells that appear during embryonic development and are responsible for producing all of the neurons in the cerebral cortex and certain lineages of glia such as astrocytes and oligodendrocytes. Newborn neurons use radial glia as scaffolds to travel along in order to reach their final destinations

• Oligodendrocytes: nonneural cells responsible for producing myelin in the CNS and maintaining the myelin sheath around the axon enabling fast salutatory conduction of action potentials as well as providing motor neurons with metabolic support.

• Schwann cells: nonneural cells responsible for producing myelin the PNS, each Schwann cell is only capable of myelinating a single axon, unlike oligodendrocytes.

Neural Membrane

The neural membrane is made up of a 4-nanometer-thick selectively permeable phospholipid bilayer. Pumps and ion channels are embedded in the protein. Only certain molecules can diffuse freely through the membrane, larger molecules pass through protein channels that open and close under specific circumstances. Selective permeability allows neurons to be polarized, meaning they have a difference in electrical charge between the inside and outside. The difference in electrical charge between two points is measured through voltage.

The polarity of a neuron is its resting potential which varies from -40 to 80mV (millivolts) but is typically ~-70mV. Electrical charge is determined by ions, atoms that have lost or gained one or more electrons. Importantly, sodium ions (Na+) and potassium ions (K+) are positively charged. Chloride ions (Cl-) are negative, as are certain proteins and amino acids that make up the organic anions (A-). The fluid outside the neuron contains mostly Na+ and Cl-, and inside is mostly K+ and A-. Therefore, the inside is mostly negative while the outside is mostly positive, making resting potential negative.

Polarity is maintained by the membrane's selective permeability combined with several forces and tools that regulate the distribution of charged ions in the neuron. The flow of charged ions in and out of the neuron is responsible for all the bioelectrical events of the neuron.

• Force of diffusion: the pressure exerted by ions from an area of greater concentration to an area of lesser concentration.

• Electrostatic pressure: the force by which like-charged ions are repelled by each other and opposite-charged ions are attracted to each other. So, ions are repelled from the side that is similarly charged and attached to the side that is oppositely charged.

• Sodium-potassium pump: large protein molecules that move sodium ions through the neuron membrane to the outside and potassium ions back inside, helping maintain the resting potential. For every two potassium ions it pumps inside the neural membrane, it removes three sodium ions.

• Ion channels: pores in the membrane formed by proteins that gate the flow of ions between the extracellular and intracellular fluids. There are three main kinds of ion channels;

  • Voltage-gated: open and close in response to changes in membrane potential

  • Ligand-gated: opens when a specific neurotransmitter latches to its receptor

  • Mechanically-gated: opens in response to the physical stretching of the membrane

Potential

When a small area of the neuron is depolarized, meaning its interior charge has shifted towards 0mV to be more positive, the partial depolarization of a neuron is referred to as local potential. Local potentials are graded and can vary in magnitude based on the strength of the signal that initiated it, they are also decremental and only effective over short distances before they die out. If the local potential exceeds the neuronal membrane threshold of -55mV, it triggers voltage-gated sodium ion channels to allow positively charged sodium ions to flood into the neuron and further depolarize the neuron.

An action potential is the all-or-nothing response that occurs when the local potential exceeds that voltage threshold. After exceeding -55mV, the neuron is abruptly depolarized and an ungraded action potential is released at full charge. If the charge does not exceed the threshold, an action potential will not fire at all. Due to this, it cannot carry information about the intensity of the initiating stimuli. Instead, the intensity of stimuli is represented by the number of neurons firing. An action potential is also nondecremental, meaning it travels down the axon without any decrease in size.

A refractory period is a state of recovery that occurs after a neuron has fired an action potential. The 1-2 millisecond duration of the absolute refractory period limits how fast the neuron can generate new action potentials. Because the ion channels behind the action potential are still recovering, the impulse can propagate only down the axon toward the dendrites, not back toward the cell body. This makes neural transmission unidirectional and prevents the neuron from locking up. There are two kinds of refractory periods;

• Absolute refractory period: the brief period following the peak of the action potential when the sodium ion channels are inactivated and the neuron cannot be fired again. During the action potential and initial recovery, the sodium ion channels are open and unresponsive to further stimulation no matter how intense.

• Relative refractory period: the period during which a neuron can be fired again following an action potential but only by an above-threshold stimulus. A stimulus that is slightly greater than the temporary higher threshold causes the neuron to fire again before the end of the relative refractory period, causing a higher fire rate — the rate law is the principle that the intensity of a stimulus is represented in an axon by the frequency of action potentials.

The neuron is limited in firing rate by the absolute refractory period and in its ability to respond to different strengths of stimuli by the all-or-none law. More intense stimuli cause the neuron to fire earlier during the relative refractory period, providing a way to encode stimulus intensity via the rate law.

Timeline: Action Potential

1. Resting potential: the neuron’s sodium and potassium channels are closed and the interior has a mostly negative charge at around -70mV.

2. Partial depolarization: the arrival of a local potential partially depolarizes the membrane.

3. Depolarization: when the local potential exceeds the neuronal membrane voltage threshold of -55mV, the voltage-gated sodium ion channels open.

4. Action potential: sodium ions rush into the neuronal membrane and quickly depolarize the membrane in that area, the membrane potential overshoots to around +30mV.

5. Repolarization: voltage-gated sodium ion channels close and voltage gates potassium ion channels open to allow positively charged potassium ions to rush out of the membrane and return the interior of the neuron to a negative state.

6. Hyperpolarization: potassium ions continue to leave the membrane, causing the membrane to become hyperpolarized at around -75mV or more.

7. Resting potential: the membrane renters resting potential with a negative charge

Neuronal Communication

• Synapse: the structure in which a neuron passes electrical or chemical signals to another neuron, muscle, or organ.

• Synaptic cleft: the small gap between a presynaptic and postsynaptic neuron.

• Presynaptic neuron: neuron that is transmitter to another.

• Postsynaptic neuron: neuron that is receiving transmissions from another.

Synapses can be electrical or chemical. At electrical synapses, electrical current (potentials) pass between the synapses through the traded flow of ions from one neuron to another. Transmission from neuron to neuron is usually chemical in vertebrates, involving neurotransmitters released onto receptors on the postsynaptic dendrites and cell body. At chemical synapses, neurotransmitters are stored in vesicles. When the action potential arrives at the terminals, it opens ion channels that allow calcium ions (Ca2+) to enter the terminals from the extracellular fluid. The calcium ions cause the vesicles close to the membrane to fuse with it and exocytosis begins, the membrane then opens and allows the transmitters to spill and diffuse into the synaptic cleft.

On the postsynaptic neuron, the neurotransmitter docks with a specialized protein that matches the molecular shape of the transmitter molecule. When the receptors are activated they open ion channels that allow ions to flow across the membrane.

• Ionotropic receptors: a receptor that forms the ion channel and opens quickly to produce immediate reactions required for muscle activity and sensory processing.

• Metabotropic receptors: a receptor on the neuron membrane that opens ion channels indirectly through a second messenger, acts slowly to produce long-lasting effects.

The effect the presynaptic neuron has on the postsynaptic neuron depends on the type of ion channels that open on the postsynaptic dendrites and soma.

• Excitatory postsynaptic potential (EPSP): an excitatory effect caused by receptors opening sodium ion channels which produce a partial depolarization, or positive change in a neural membrane’s voltage, and makes action potentials more likely to occur by bringing its membrane closer to the threshold of -55mV.

• Inhibitory postsynaptic potential (IPSP): an inhibitory effect caused by receptors opening potassium in channels, chloride channels, or both, and causes hyperpolarization as potassium moves out or chloride moves in, which makes action potentials less likely to occur.

EPSPs and IPSPs cause a graded local potential that travels down the neuron to the axon hillock, increasing and decreasing the neuron’s baseline rate of spontaneous action potential generation respectively. A positive graded potential that surpasses the threshold will produce an action potential; a negative graded potential will make it less likely to be generated. Depending on if the net sum of excitatory and inhibitory signals surpasses the voltage threshold, the neuron will either fire an action potential or not.

Postsynaptic Integration

A typical neuron receives input from approximately 1,000 other neurons. Because a single neuron has a relatively small effect, the postsynaptic neuron must combine potentials from many neurons to fire — ensuring the neuron will not be fired by the spontaneous activity of a single presynaptic neuron and allowing the neuron to combine multiple inputs into more complex messages. These potentials are combined at the axon hillock in two ways;

• Spatial summation: combines potentials occurring simultaneously at different locations on the dendrites and cell body.

• Temporal summation: combines potentials arriving a short time apart, forming either the same or separate inputs. This is possible because a local potential persists for a few milliseconds.

The summation of EPSPs makes action potentials more likely to occur. Summation of IPSPs drives the membrane’s interior to be even more negative and inhibits the signals of incoming EPSPs to trigger an action potential. When both excitatory and inhibitory impulses arrive on a neuron, they will summate algebraically.

Terminating Synaptic Activity

Typically, neurotransmitters must be inactivated. They are usually taken back into the terminals by transporter membrane proteins in the process of reuptake. The transmitters are then repackaged in vesicles to be used again. In some synapses, the transmitter in the synaptic cleft is absorbed by nearby astrocytes. In others, transmitters are partially broken down through the process of inactivation, typically dissolved by enzymes.

Regulating Synaptic Activity

The nervous system controls complex behavior and must have several ways to regulate synaptic activity. At axoaxonic synapses, a third neuron releases transmitters onto the terminals of the presynaptic neuron which causes presynaptic excitation or presynaptic inhibition. One way an axoaxonic synapse can adjust a presynaptic terminals activity is by regulating the amount of calcium entering the terminal which triggers neurotransmitter release.

• Presynaptic excitation: increases the presynaptic neuron’s release of neurotransmitters onto the postsynaptic neuron.

• Presynaptic inhibition: decreases the presynaptic neuron’s release of neurotransmitters onto the postsynaptic neuron.

Neurons can regulate their own synaptic activity in two ways;

• Autoreceptors: autoreceptors are receptors on a neuron’s terminal that senses the amount of transmitter in the synaptic cleft and reduces the presynaptic neuron’s output when the level is excessive. When there are unusually increases or decreases in neurotransmitter release, postsynaptic receptors change their sensitivity or even their numbers to compensate.

• Glia: Glial cells are active partners in neural transmission and regulation of synaptic activity. They surround the synapse and prevent neurotransmitters from spreading to other synapses. Some can remove neurotransmitters from the synaptic cleft and recycle it for the neuron’s reuse. They can influence postsynaptic excitability by varying the amount of transmitter they remove, as well as respond to neurotransmitter levels in the synapse by releasing their own transmitter. Gliotransmitters regulate transmitter release from the presynaptic neuron or directly stimulate the postsynaptic neuron to excite or inhibit.

Neurotransmitters

Having a variety of neurotransmitters multiplies the effects that can be produced at synapses; there are different subtypes of the receptors that adds even more variety. Contrary to the outdated Dale’s principle that states a neuron is only capable of releasing a single transmitter, neurons can release more than one or two type of neurotransmitter. Some can release one transmitter in response to a weak stimulation and another to a strong stimulation.

• Acetylcholine: transmitter at muscles; in brain, involved in learning, etc.

Monoamines — a compound having a single amine (compounds containing a basic nitrogen atom with a lone pair) group in its molecule

• Serotonin: Involved in mood, sleep and arousal, aggression, depression, obsessive-compulsive disorder, and alcoholism.

• Dopamine: Contributes to movement control and promotes reinforcing effects of food, sex, and abused drugs. Dysregulation is involved in schizophrenia and Parkinson’s disease.

• Norepinephrine: A hormone released during stress. Functions as a neurotransmitter in the brain to increase arousal and attentiveness to events in the environment. Diminished norepinephrine transmission is involved in depression.

• Epinephrine: A stress hormone related to norepinephrine; plays a minor role as a neurotransmitter in the brain.

Amino acids — organic compounds that make up proteins and perform specialized functions in the body

• Glutamate: The principal excitatory neurotransmitter in the brain and spinal cord. Vitally involved in learning; glutamate dysfunction is implicated in schizophrenia.

• Gamma-aminobutyric acid (GABA): The predominant inhibitory neurotransmitter. Its receptors respond to alcohol and the class of tranquilizers called benzodiazepines. Deficiency in GABA or receptors is one cause of epilepsy.

• Glycine: Inhibitory transmitter in the spinal cord and lower brain. The poison strychnine causes convulsions and death by affecting glycine activity.

Neuropeptides — any of a group of compounds that act as neurotransmitters and are short-chain polypeptides (a linear organic polymer (a substance with a molecular structure consisting primarily of many large similar molecules bonded together) composed of lots of amino acid residues bonded together in a chain forming part of or a whole protein molecule)

• Endorphins: Neuromodulators that reduce pain and enhance reinforcement.

• Substance P: Transmitter in neurons sensitive to pain.

• Neuropeptide Y: Initiates eating and produces metabolic shifts.

Gas — gaseous neurotransmitters, or gasotransmitters, are small gaseous molecules that function as neurotransmitters. Not stored in secretory vesicles but are produced when required.

• Nitric oxide: One of two known gaseous transmitters, along with carbon monoxide. Can serve as a retrograde transmitter, influencing the presynaptic neuron’s release of neurotransmitter. Viagra enhances male erections by increasing nitric oxide’s ability to relax blood vessels and produce penile engorgement.

Transmitter release from the neuron can occur in three ways;

• Corelease: transmitters are packaged int he same vesicle. They are not always released equally, sometimes fusion pores can only partially open and allow smaller molecules to exit freely while impeding the release of larger ones.

• Cotransmission: transmitter are in separate vesicles. Transmitters each differ in sensitivity to calcium (Ca2+), therefore a low rate of neural impulses will trigger release of only one messenger and a higher rate will release both.

• Cotransmission — spatial segregation: transmitter are packaged in separate terminals to produce different effects at separate destinations.

Neural Codes and Networks

Neurons produce electrical impulses that carry in intervals and lengths, varying firing patterns. The specific firing patterns produce specific neural activity through coding, which is read and used by the brain.

Neural networks are groups of neurons that function together to carry out a process. This is where the most complex neural processing occurs, such as identifying objects, performing language functions, and producing conscious awareness. The Human Connectome Project is a large-scale cooperative effort to map the circuits in the human brain. Mapping a roundworm brain, composed of just 300 neurons and 7,00 connections, took over a decade.